Expression of Surfactant Protein D Distinguishes Severe Pandemic Influenza A(H1N1) from Coronavirus Disease 2019.

The differentiation between influenza and coronavirus disease 2019 (COVID-19) could constitute a diagnostic challenge during the ongoing winter owing to their clinical similitude. Thus, novel biomarkers are required to enable making this distinction. Here, we evaluated whether the surfactant protein D (SP-D), a collectin produced at the alveolar epithelium with known immune properties, was useful to differentiate pandemic influenza A(H1N1) from COVID-19 in critically ill patients. Our results revealed high serum SP-D levels in patients with severe pandemic influenza but not those with COVID-19. This finding was validated in a separate cohort of mechanically ventilated patients with COVID-19 who also showed low plasma SP-D levels. However, plasma SP-D levels did not distinguish seasonal influenza from COVID-19 in mild-to-moderate disease. Finally, we found that high serum SP-D levels were associated with death and renal failure among severe pandemic influenza cases. Thus, our studies have identified SP-D as a unique biomarker expressed during severe pandemic influenza but not COVID-19.

Common hematological values predict unfavorable outcomes in hospitalized COVID-19 patients.

COVID-19 can range from asymptomatic to life-threatening. Early identification of patients who will develop severe disease is crucial. A number of scores and indexes have been developed to predict severity. However, most rely on measurements not readily available. We evaluated hematological and biochemical markers taken on admission and determined how predictive they were of development of critical illness or death. We observed that higher values of readily available tests, including neutrophil:lymphocyte ratio; derived neutrophil index; and troponin I were associated with a higher risk of death or critical care admission (P < 0.001). We show that common hematological tests can be helpful in determining early in the course of illness which patients are likely to develop severe forms, as well as allocating resources to those patients early, while avoiding overuse of limited resources in patients with reduced risk of progression to severe disease.

Changes in Radial Artery Pulse Pressure During a Fluid Challenge Cannot Assess Fluid Responsiveness in Patients With Septic Shock.

BACKGROUND: Arterial blood pressure is the most common variable used to assess the response to a fluid challenge in routine clinical practice. The aim of this study was to evaluate the accuracy of the change in the radial artery pulse pressure (rPP) to detect the change in cardiac output after a fluid challenge in patients with septic shock. METHODS: Prospective observational study including 35 patients with septic shock in which rPP and cardiac output were measured before and after a fluid challenge with 400 mL of crystalloid solution. Cardiac output was measured with intermittent thermodilution technique using a pulmonary artery catheter. Patients were divided between responders (increase >15% of cardiac output after fluid challenge) and nonresponders. The area under the receiver operating characteristic curve (AUROC), Pearson correlation coefficient and paired Student t test were used in statistical analysis. RESULTS: Forty-three percent of the patients were fluid responders. The change in rPP could not neither discriminate between responders and nonresponders (AUROC = 0.52; [95% confidence interval: 0.31-0.72] P = .8) nor correlate (r = .21, P = .1) with the change in cardiac output after the fluid challenge. CONCLUSIONS: The change in rPP neither discriminated between fluid responders and nonresponders nor correlated with the change in cardiac output after a fluid challenge. The change in rPP cannot serve as a surrogate of the change in cardiac output to assess the response to a fluid challenge in patients with septic shock.

CLINICAL AND EPIDEMIOLOGICAL CHARACTERISTICS OF PATIENTS DIAGNOSED WITH COVID-19 IN A TERTIARY CARE CENTER IN MEXICO CITY: A PROSPECTIVE COHORT STUDY.

BACKGROUND: Regional information regarding the characteristics of patients with coronavirus disease (COVID)-19 is needed for a better understanding of the pandemic. OBJECTIVE: The objective of the study to describe the clinical features of COVID-19 patients diagnosed in a tertiary-care center in Mexico City and to assess differences according to the treatment setting (ambulatory vs. hospital) and to the need of intensive care (IC). METHODS: We conducted a prospective cohort, including consecutive patients with COVID-19 from February 26, 2020 to April 11, 2020. RESULTS: We identified 309 patients (140 inpatients and 169 outpatients). The median age was 43 years (interquartile range, 33-54), 59.2% men, and 18.6% healthcare workers (12.3% from our center). The median body mass index (BMI) was 29.00 kg/m2 and 39.6% had obesity. Compared to outpatients, inpatients were older, had comorbidities, cough, and dyspnea more frequently. Twenty-nine (20.7%) inpatients required treatment in the IC unit (ICU). History of diabetes (type 1 or 2) and abdominal pain were more common in ICU patients compared to non-ICU patients. ICU patients had higher BMIs, higher respiratory rates, and lower room-air capillary oxygen saturations. ICU patients showed a more severe inflammatory response as assessed by white blood cell count, neutrophil and platelet count, C-reactive protein, ferritin, procalcitonin, and albumin levels. By the end of the study period, 65 inpatients had been discharged because of improvement, 70 continued hospitalized, and five had died. CONCLUSIONS: Patients with comorbidities, either middle-age obese or elderly complaining of fever, cough, or dyspnea, were more likely to be admitted. At admission, patients with diabetes, high BMI, and clinical or laboratory findings consistent with a severe inflammatory state were more likely to require IC.

Pulmonary Vasoreactivity and Phenotypes in Pulmonary Arterial Hypertension Associated to Connective Tissue Diseases.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a fatal complication in patients with connective tissue disease (CTD). OBJECTIVE: The objective of the study was to study the prognostic value of the acute pulmonary vasoreactivity test with inhaled iloprost and its association with clinical deterioration in a tertiary care academic medical center. METHODS: We conducted a prospective study of patients with CTD and the diagnosis of PAH established by right heart catheterization. Patients were classified into classic responders, partial responders, and non-responders. The association of the pulmonary response and clinical deterioration was analyzed. RESULTS: We enrolled 25 patients (mean age of 47 ± 13.4 years); 88% were female. The most frequent rheumatologic diagnosis was systemic lupus erythematosus, in 16 (64%) patients. Seventy-two percent of patients were classified as non-responders, and 28% were partial responders. Patients with a partial response had lower right atrial pressure values (5.1 ± 3.1 vs. 8.5 ± 3.2, p = 0.01) and greater systolic pulmonary arterial pressure (87.6 ± 8.1 vs. 72.4 ± 16.2, p = 0.02), compared with non-responders. Non-responders had a tendency for a shorter time to clinical deterioration than partial responders (17.8 vs. 41.1 months, p = 0.052). CONCLUSIONS: Patients with a partial response to the acute pulmonary vasodilator test with inhaled iloprost had a longer clinical deterioration-free period than non-responders.

The 2009 pandemic in Mexico: Experience and lessons regarding national preparedness policies for seasonal and epidemic influenza.

Influenza is a viral respiratory disease capable of causing epidemics that represent a threat for global security. Mexico was the first country to notify the WHO of an outbreak of what later became the first influenza pandemic of the 21st Century, caused by the virus A(H1N1)2009. Before this event Mexico had a national pandemic influenza preparedness plan, which included seasonal influenza vaccination, stockpiles of personal protection equipment and strategic drugs, and risk communication strategies. During the epidemic, the national public health laboratory network and case surveillance systems were strengthened together with surge capacities for intensive care and delivery of antiviral drugs. Risk communication was conducted for people to comply with implemented measures regarding social distancing (workplace and school closures, household quarantine). This report describes the Mexican experience during the 2009 influenza pandemic and the lessons that this experience provides to public health preparedness for future pandemics.

Influenza A (H1N1pdm09)-Related Critical Illness and Mortality in Mexico and Canada, 2014.

OBJECTIVES: The 2009-2010 influenza A (H1N1pdm09) pandemic caused substantial morbidity and mortality among young patients; however, mortality estimates have been confounded by regional differences in eligibility criteria and inclusion of selected populations. In 2013-2014, H1N1pdm09 became North America's dominant seasonal influenza strain. Our objective was to compare the baseline characteristics, resources, and treatments with outcomes among critically ill patients with influenza A (H1N1pdm09) in Mexican and Canadian hospitals in 2014 using consistent eligibility criteria. DESIGN: Observational study and a survey of available healthcare setting resources. SETTING: Twenty-one hospitals, 13 in Mexico and eight in Canada. PATIENTS: Critically ill patients with confirmed H1N1pdm09 during 2013-2014 influenza season. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The main outcome measures were 90-day mortality and independent predictors of mortality. Among 165 adult patients with H1N1pdm09-related critical illness between September 2013 and March 2014, mean age was 48.3 years, 64% were males, and nearly all influenza was community acquired. Patients were severely hypoxic (median PaO2-to-FIO2 ratio, 83 mm Hg), 97% received mechanical ventilation, with mean positive end-expiratory pressure of 14 cm H2O at the onset of critical illness and 26.7% received rescue oxygenation therapy with prone ventilation, extracorporeal life support, high-frequency oscillatory ventilation, or inhaled nitric oxide. At 90 days, mortality was 34.6% (13.9% in Canada vs 50.5% in Mexico, p < 0.0001). Independent predictors of mortality included lower presenting PaO2-to-FIO2 ratio (odds ratio, 0.89 per 10-point increase [95% CI, 0.80-0.99]), age (odds ratio, 1.49 per 10 yr increment [95% CI, 1.10-2.02]), and requiring critical care in Mexico (odds ratio, 7.76 [95% CI, 2.02-27.35]). ICUs in Canada generally had more beds, ventilators, healthcare personnel, and rescue oxygenation therapies. CONCLUSIONS: Influenza A (H1N1pdm09)-related critical illness still predominantly affects relatively young to middle-aged patients and is associated with severe hypoxemic respiratory failure. The local critical care system and available resources may be influential determinants of patient outcome.

[The process of death in the intensive care unit (ICU). From a medical, thanatological and legislative point of view]. / El proceso de muerte en la unidad de cuidados intensivos (UCI). Punto de vista médico, tanatológico y legislativo.

Traditional goals in the intensive care unit are to reduce morbidity and mortality. Despite medical and technological advances, death in the intensive care unit remains commonplace and the modern critical care team should be familiar with palliative care and legislation in Mexico. Preserving the dignity of patients, avoiding harm, and maintaining communication with the relatives is fundamental. There is no unique, universally accepted technical approach in the management of the terminal critical care patient, so it is important to individualize each case and define objectives together under the legal framework in Mexico.

[Pulmonary hypertension associated with connective tissue diseases]. / Hipertensión arterial pulmonar por ecocardiografía en pacientes con enfermedades de tejido conectivo.

BACKGROUND: Pulmonary arterial hypertension is an important cause of complications among patients with connective tissue diseases. AIM: To describe the clinical and echocardiographic characteristics of patients with pulmonary hypertension associated with connective tissue diseases. MATERIAL AND METHODS: Retrospective, observational and descriptive study. We analyzed 35 patients with pulmonary hypertension associated with connective tissue diseases. All patients were evaluated and diagnosed by at least one medical specialist in rheumatology. Pulmonary arterial hypertension was defined as a pulmonary artery systolic pressure ≥ 40 mmHg by echocardiography. The group was divided as not severe when pressures ranged from 40 to 64 mmHg and severe, when pressures were ≥ 65 mmHg. RESULTS: The most common connective tissue disease associated with pulmonary arterial hypertension was diffuse scleroderma in 46% of cases. Eighty nine percent of patients were female. Time of evolution of the pulmonary hypertension was 18.8 ± 21.8 months. The distance walked in the six minute walk test was < 400 m both in patients with and without severe pulmonary hypertension. Fifty one percent of patients had pulmonary restriction. No differences in gas exchange parameters were observed between groups. Comparing echo cardio-graphic findings in patients with and without severe hypertension, the former had a higher frequency of right ventricular dilatation (85.7 and 52.3% respectively, p = 0.04), right ventricular hypertrophy (42.8 and 0% respectively, p = 0.02) and right ventricular hypokinesia (71.4 and 9.5% respectively p = < 0.01). CONCLUSIONS: Patients with severe pulmonary arterial hypertension associated to connective tissue diseases have more commonly dilated, hypertrophic and hypokinetic right ventricles.

A 39-Year-Old Man With an Arteriovenous Malformation With New Dyspnea and Lower Limb Edema.

CASE PRESENTATION: A 39-year-old man with a history of arteriovenous malformation in the upper right limb that was complicated with vascular-type ulcers and repeated soft tissue infection and who had needed a supracondylar amputation of the limb when he was 27 years old presented a new soft tissue infection that manifested with fever, chills, increase in the diameter of the stump with local skin erythema, and painful necrotic ulcers. The patient reported mild dyspnea for 3 months (World Health Organization functional class II/IV) that had worsened during the last week (World Health Organization functional class III/IV) with chest tightness and bilateral lower limb edema.

[Survey about responsiveness of third-level hospitals to a medical disaster: after the pandemic influenza in Mexico]. / Encuesta sobre la capacidad de respuesta de los hospitales de alta especialidad ante un desastre médico: después de la influenza pandémica en México.

BACKGROUND: The recent pandemic influenza AH1N1 virus made it clear that planning for medical disaster response is critical. OBJECTIVE: To know the responsiveness of a sample of highly specialized hospitals in Mexico to a medical disaster, with the previous pandemic influenza AH1N1 as reference. METHODS: A survey was conducted among the Medical Directors of a sample of highly specialized hospitals, covering: previous experience with the pandemic influenza, space considerations, material resources, staff, logistics, and current general perspectives. Descriptive statistics were used for analysis. RESULTS: A 95% response was obtained from the institutions (19 hospitals). Of these, 47.4% considered that the medical institution was not ready to respond to pandemic influenza. The median surge capacity for the Intensive Care Unit beds was 30% (range 0 to 32 beds). The least reserve in medication was found in the antivirals (26.3%). Only 47.4% considered having enough intensive care nurses and 57.9% enough respiratory technicians; 42.1% would not have an easy access to resources in an emergency. CONCLUSIONS: Prevention is key in responsiveness to medical disasters, and therefore the basic steps for planning strategies must be considered.

Clinicopathologic characteristics of severe COVID-19 patients in Mexico City: A post-mortem analysis using a minimally invasive autopsy approach.

OBJECTIVE: Describe the histological findings of minimally ultrasound-guided invasive autopsies in deceased patients with severe SARS-CoV-2 and compare the diagnostic yield with open autopsies. DESIGN: Observational post-mortem cohort study. Minimally invasive ultrasound-guided autopsies were performed in fourteen deceased patients with a confirmed diagnosis of SARS-CoV-2 pneumonia. Histological and clinical findings of lung, kidney, and liver tissue are described and contrasted with those previously reported in the literature. SETTING: Single-center COVID-19 reference center in Mexico City. RESULTS: Fourteen minimally invasive autopsies revealed a gross correlation with open autopsies reports: 1) Lung histology was characterized mainly by early diffuse alveolar damage (12/13). Despite low lung compliances and prolonged mechanical ventilation, the fibrotic phase was rarely observed (2/13). 2) Kidney histopathology demonstrated acute tubular injury (12/13), interstitial nephritis (11/13), and glomerulitis (11/13) as the predominant features 3) Liver histology was characterized by neutrophilic inflammation in all of the cases, as well as hepatic necrosis (8/14) despite minimal alterations in liver function testing. Hepatic steatosis was observed in most cases (12/14). SARS-CoV-2 positivity was widely observed throughout the immunohistochemical analysis. However, endothelitis and micro thrombosis, two of the hallmark features of the disease, were not observed. CONCLUSION: Our data represents the largest minimally invasive, ultrasound-guided autopsy report. We demonstrate a gross histological correlation with large open autopsy cohorts. However, this approach might overlook major histologic features of the disease, such as endothelitis and micro-thrombosis. Whether this represents sampling bias is unclear.

Outcomes in Temporary ICUs Versus Conventional ICUs: An Observational Cohort of Mechanically Ventilated Patients With COVID-19-Induced Acute Respiratory Distress Syndrome.

Throughout the COVID-19 pandemic, thousands of temporary ICUs have been established worldwide. The outcomes and management of mechanically ventilated patients in these areas remain unknown. OBJECTIVES: To investigate mortality and management of mechanically ventilated patients in temporary ICUs. DESIGN SETTING AND PARTICIPANTS: Observational cohort study in a single-institution academic center. We included all adult patients with severe COVID-19 hospitalized in temporary and conventional ICUs for invasive mechanical ventilation due to acute respiratory distress syndrome from March 23, 2020, to April 5, 2021. MAIN OUTCOMES AND MEASURES: To determine if management in temporary ICUs increased 30-day in-hospital mortality compared with conventional ICUs. Ventilator-free days, ICU-free days (both at 28 d), hospital length of stay, and ICU readmission were also assessed. RESULTS: We included 776 patients (326 conventional and 450 temporary ICUs). Thirty-day in-hospital unadjusted mortality (28.8% conventional vs 36.0% temporary, log-rank test p = 0.023) was higher in temporary ICUs. After controlling for potential confounders, hospitalization in temporary ICUs was an independent risk factor associated with mortality (hazard ratio, 1.4; CI, 1.06-1.83; p = 0.016).There were no differences in ICU-free days at 28 days (6; IQR, 0-16 vs 2; IQR, 0-15; p = 0.5) or ventilator-free days at 28 days (8; IQR, 0-16 vs 5; IQR, 0-15; p = 0.6). We observed higher reintubation (18% vs 12%; p = 0.029) and readmission (5% vs 1.6%; p = 0.004) rates in conventional ICUs despite higher use of postextubation noninvasive mechanical ventilation (13% vs 8%; p = 0.025). Use of lung-protective ventilation (87% vs 85%; p = 0.5), prone positioning (76% vs 79%; p = 0.4), neuromuscular blockade (96% vs 98%; p = 0.4), and COVID-19 pharmacologic treatment was similar. CONCLUSIONS AND RELEVANCE: We observed a higher 30-day in-hospital mortality in temporary ICUs. Although both areas had high adherence to evidence-based management, hospitalization in temporary ICUs was an independent risk factor associated with mortality.

Mesenchymal Stem Cells for the Compassionate Treatment of Severe Acute Respiratory Distress Syndrome Due to COVID 19.

Mesenchymal stem cells (MSC) have received particular attention due to their ability to inhibit inflammation caused by cytokine storm induced by COVID-19. In this way some patients have been treated successfully. The aim of this study was to evaluate the safety and describe the clinical changes after IV administration of allogeneic human umbilical cord MSC (ahUCMSC), in patients with bilateral pneumonia caused by COVID-19, complicated with severe ARDS, as compassionate treatment. This was a pilot, open-label, prospective, longitudinal study. Five patients that did not improve in their clinical conditions after 48 hours of receiving the standard medical management used by the Medical Center and with persistent PaO2/FiO2 less than 100 mmHg were enrolled. ahUCMSC were infused IV, at dose of 1x106 per Kg of body weight over 15 minutes. Patients were monitored after the infusion to detect adverse event. Pa02/FiO2, vital signs, D-dimer, C reactive protein and total lymphocytes were monitored for 21 days after the infusion or until the patient was discharged from the hospital. Descriptive statistics were used with means or medians and standard deviation or interquartile range according to the type of variable. The Wilcoxon's rank-sum was used for stationary samples. Adverse events occurred in three patients and were easily and quickly controlled. Immediately after the infusion of ahUCMSC, constant rise of PaO2/FiO2 was observed in all patients during the first 7 days, with statistical significance. Three patients survived and were extubated on the ninth day post-infusion. Two patients died at 13 and 15 days after infusion. The infusion of ahUCMSC in patients with severe ARDS caused by COVID-19, was safe, and demonstrated its anti-inflammatory capacity in the lungs, by improving the respiratory function expressed by PaO2 / FiO2, which allowed the survival of 3 patients, with extubation at 9 days.

Educative Hybrid Intervention as a Strategy for Reintegration to the Clinical Courses of Undergraduate Students in COVID-19 Pandemic.

The SARS-CoV-2 pandemic generated the need to modify the current clinical educational model with the challenge of promoting safety and the continuity of clinical education through the use of virtual platforms. Since clinical training in hospital institutions cannot be substituted, a strategic training plan was developed to guarantee protection, safety, and academic continuity for students upon returning to clinical clerkships. The objective of this project was to develop and evaluate the impact of a massive hybrid training plan as an educative strategy to give the theoretical and practical knowledge required for the safe return of undergraduate students to their respective clinical activities in the context of this pandemic. An academic program was designed through a massive hybrid strategy to train 616 undergraduate students studying clinical cycles by presential, virtual, synchronous, and asynchronous activities. To know the program's impact, a study based on an initial evaluation and a final evaluation was carried out to evaluate the acquisition of the critical knowledge and skills of the program. A significant difference was found between the means of the initial and final evaluations (p <0.001), as well as a high impact of the intervention (d 1.6). Significant improvements in the areas of COVID-19 initial management (p <0.001) and personal protective equipment use (p <0.001) were seen in the post-test when compared to the initial evaluation. Both a quantitative and a qualitative analysis were carried out, finding positive results on the course design, quality of didactic resources, and instructors' performance. Massive hybrid training is an effective strategy to facilitate the reintegration of undergraduate students into their face-to-face clinical rotations.

Outcomes of patients with COVID-19 in the intensive care unit in Mexico: A multicenter observational study.

BACKGROUND: As of June 15, 2020, a cumulative total of 7,823,289 confirmed cases of COVID-19 have been reported across 216 countries and territories worldwide. However, there is little information on the clinical characteristics and outcomes of critically ill patients with severe COVID-19 who were admitted to intensive care units (ICUs) in Latin America. The present study evaluated the clinical characteristics and outcomes of critically ill patients with severe COVID-19 who were admitted to ICUs in Mexico. METHODS: This was a multicenter observational study that included 164 critically ill patients with laboratory-confirmed COVID-19 who were admitted to 10 ICUs in Mexico, from April 1 to April 30, 2020. Demographic data, comorbid conditions, clinical presentation, treatment, and outcomes were collected and analyzed. The date of final follow-up was June 4, 2020. RESULTS: A total of 164 patients with severe COVID-19 were included in this study. The mean age of patients was 57.3 years (SD 13.7), 114 (69.5%) were men, and 6.0% were healthcare workers. Comorbid conditions were common in patients with critical COVID-19: 38.4% of patients had hypertension and 32.3% had diabetes. Compared to survivors, nonsurvivors were older and more likely to have diabetes, hypertension or other conditions. Patients presented to the hospital a median of 7 days (IQR 4.5-9) after symptom onset. The most common presenting symptoms were shortness of breath, fever, dry cough, and myalgias. One hundred percent of patients received invasive mechanical ventilation for a median time of 11 days (IQR 6-14). A total of 139 of 164 patients (89.4%) received vasopressors, and 24 patients (14.6%) received renal replacement therapy during hospitalization. Eighty-five (51.8%) patients died at or before 30 days, with a median survival of 25 days. Age (OR, 1.05; 95% CI, 1.02-1.08; p<0.001) and C-reactive protein levels upon ICU admission (1.008; 95% CI, 1.003-1.012; p<0.001) were associated with a higher risk of in-hospital death. ICU length of stay was associated with reduced in-hospital mortality risk (OR, 0.89; 95% CI, 0.84-0.94; p<0.001). CONCLUSIONS: This observational study of critically ill patients with laboratory-confirmed COVID-19 who were admitted to the ICU in Mexico demonstrated that age and C-reactive protein level upon ICU admission were associated with in-hospital mortality, and the overall hospital mortality rate was high. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04336345.

H1N1 Influenza Pandemic of 2009 Compared With Other Influenza Pandemics: Epidemiology, Diagnosis, Management, Pulmonary Complications, and Outcomes.

Influenza pandemics are complex events that have occurred frequently throughout human history, three during the past century alone. Now the world is facing the first 21st century pandemic, and the comparison among them is essential to identify common epidemiologic patterns, clinical characteristics, and outcomes. The evolution of medicine, including diagnostic and treatment options, the critical care advances, and global responses are new interventions that could modify the general outcome of the pandemic. Learning from past and current events could lead to a plan for prompt and efficient response in future pandemics and may be help us to predict the unpredictable.